DNA methylation represents an important layer of epigenetic regulation on the activity of the human genome. It is well known that there is a tremendous amount of genetic variation among human individuals and populations. Such genetic variation leads to the variation of gene expression among different individuals for the same cell types or tissues. Accumulating evidence suggests that the epigenome, including methylome, also varies from one individual to another. Such variation is believed to play functional roles in the individual variation of a variety of phenotypes, including many human diseases. Yet the detailed mechanisms and the extent to which the epigenome is individualized by the ensemble of genetic polymorphisms remains barely investigated. We will comprehensively characterize the effects of genetic polymorphisms on the individual human methylomes. The ultimate goal of this study is to understand how DNA methylation is organized along single human chromosomes, how do such local or long-range organizations relate to the functions, and how do genetic variations affect the functional organization of DNA methylation. The specific aims are: (1) Experimentally construction of fully phased diploid human genomes, which will serve as a chassis to connect short and long range cis-regulators of DNA methylation, and to link methylation to the binding of protein cis-regulators as well as gene expression. (2) Mapping cis-regulatory variants for DNA methylation by integrating mQTL associative mapping with allele-specific methylation analysis. This proposed study will produce a method for constructing phased diploid methylome and an analytic framework for studying long-range genetic regulation of the DNA methylome. We will identify a list of cis-regulatory variants in the HapMap samples used in this study. The experimental and analytical framework will be applicable to the study of the genetic effects on a variety of other epigenetic modifications.